Cocaine dependence remains a significant health issue in the United States, with recent surveys indicating that more than 5.6 million Americans had used cocaine within the past year, and more than 23 million at some time in their lifetimes. Interestingly, estimates indicate that only about 5 to 10 percent of those who use cocaine eventually become dependent on it. Reportedly, a typical pattern of development of cocaine dependence is one in which a person uses the drug intermittently for a period of two to four years before full-fledged dependence emerges. The factors that lead to dependence have not been identified, so the proposed research is aimed at furthering our knowledge concerning behavioral effects of relatively long-term intermittent exposure to cocaine. Laboratory study of effects of intermittent exposure to cocaine has revealed either tolerance or sensitization. Previous research, however, has indicated that experiential/behavioral factors can determine whether or not tolerance to cocaine's effects occurs. The proposed research is aimed at adding to our knowledge of how experiential factors interact with repeated cocaine exposure. The specific aims of this application are to: 1.) Expand our analyses of the interaction between explicitly conditioned operant behavior (as a model of purposive behavior) and general activity (while characterizing activity more fully) during repeated exposure to cocaine. Our recent finding that presence of an operant contingency prevented the observation of sensitization to the drug's effects on general activity has set the basis for this aim. 2.) Continue our examination of the role of alterations in rate of reinforcement as a predictor of tolerance to effects of cocaine. 3.) Continue analyses of reinforcement-schedule-parameter dependent tolerance to determine if such tolerance is "contingent," if and how it is related to behavioral economic factors, and how rate of reinforcement and ratio contingencies interact. The study of long-term, intermittent exposure to cocaine has clear potential relevance to the genesis of cocaine dependence. Understanding of the processes that occur under long-term, intermittent exposure should facilitate the development of effective treatment and, especially, prevention programs.